Biomarkers for the diagnosis, prognosis, assessment and therapy stratification of syncope

Abstract

The present invention relates to a method for the diagnosis and/or prognosis and/or assessment and/or therapy stratification of syncope in a patient the method comprising: determining the level of at least one biomarker selected from the group consisting of proET-1, pro ADM, proANP, proBNP, proAVP and PCT or a fragment of at least 12 amino acids thereof, in a sample of a bodily fluid of said patient, correlating said level of at least one biomarker or fragments thereof with the diagnosis and/or prognosis and/or assessment and/or therapy stratification of syncope.

1 . A method for the diagnosis and/or prognosis and/or assessment and/or therapy stratification of syncope in a patient the method comprising:
 determining the level of at least one biomarker selected from the group consisting of proET-1, proADM, proANP, proBNP, proAVP and PCT or a fragment of at least 12 amino acids thereof, in a sample of a bodily fluid of said patient,   correlating said level of at least one biomarker or fragments thereof with the diagnosis and/or prognosis and/or assessment and/or therapy stratification of syncope.   
     
     
         2 . The method according to  claim 1 , wherein the sample is taken at baseline before the start of an orthostatic tolerance test, preferably the HUT test or active standing test. 
     
     
         3 . The method according to  claim 1 , wherein at least one sample of a bodily fluid of said patient is taken during or after an orthostatic tolerance test. 
     
     
         4 . The method according to  claim 1 , wherein the levels of at least one biomarker or fragments thereof are determined in at least two samples of a bodily fluid of said patient taken at baseline before the start and during or after an orthostatic tolerance test. 
     
     
         5 . The method according to  claim 1 , wherein the levels of the at least one biomarker or fragments thereof are combined in a mathematical algorithm. 
     
     
         6 . The method according to  claim 1 , wherein the at least one level of at least one biomarker is combined with at least one clinical parameter selected from the group consisting of age, gender, body mass index (BMI), systolic blood pressure, diastolic blood pressure, heart rate, glomerular filtration rate (GFR), total cholesterol, HDL-cholesterol, age, gender, number of syncopal attacks and the time from the first onset of syncopal attacks. 
     
     
         7 . The method according to  claim 1 , wherein a differential diagnosis is carried out for at least two of the diseases which are selected from the group consisting of neurally-mediated syncope (NMS), orthostatic hypotension and cardiac syncope. 
     
     
         8 . The method according to  claim 7 , wherein the NMS is selected from the group consisting of VVS, CSH, vasodepressor reflex, cardioinhibitory reflex and mixed reflex. 
     
     
         9 . The method according to  claim 7 , wherein the orthostatic hypotension is selected from the group consisting of initial OH, classical OH, delayed (progressive) OH and POTS. 
     
     
         10 . The method according to  claim 7 , wherein the cardiac syncope is selected from cardiac syncope due to arrhythmia and cardiac syncope due to a structural disease. 
     
     
         11 . The method according to  claim 1 , wherein the sample is selected from the group comprising a blood sample, a serum sample, a plasma sample, a cerebrospinal fluid sample, a saliva sample and a urine sample or an extract of any of the aforementioned samples. 
     
     
         12 . The method according to  claim 1 , wherein the level of a precursor fragment, selected from the group consisting of MR-proADM, NT-proBNP, BNP, MR-proANP, Copeptin, CT-proET-1, PCT 1-116, PCT 2-116 or PCT 3-116, is determined. 
     
     
         13 . The method according to  claim 1 , wherein the patient is diagnosed with not having orthostatic hypotension when said determined CT-proET-1 level at baseline is lower than a predetermined threshold level. 
     
     
         14 . The method according to  claim 1 , wherein the patient is diagnosed with not having CSH when said determined MR-proANP level at baseline is higher than a predetermined threshold level. 
     
     
         15 . The method according to  claim 1 , wherein the patient is diagnosed with not having cardioinhibitory reflex when said determined CT-proET-1 level at baseline is higher than a predetermined threshold level. 
     
     
         16 . The method according to  claim 1 , wherein the patient is diagnosed with not having initial OH when said determined CT-proAVP level at baseline is higher than a predetermined threshold level. 
     
     
         17 . The method according to  claim 1 , wherein the patient is diagnosed with not having a vasovagal syncope when said determined MR-proANP level at baseline is higher than a predetermined threshold level. 
     
     
         18 . The method according to  claim 12 , wherein MR-proADM is detected by a sandwich immunoassay using a first antibody directed against a peptide comprising the amino acids 68 to 86 of the human preproADM sequence (SEQ ID NO: 5) and a second antibody directed against a peptide comprising the amino acids 83 to 94 of the human preproADM sequence (SEQ ID NO: 5). 
     
     
         19 . The method according to  claim 12 , wherein CT-proET-1 is detected by a sandwich immunoassay using a first antibody directed against a peptide comprising the amino acids 167 to 183 of the human proET-1 sequence (SEQ ID NO: 18) and a second antibody directed against a peptide comprising the amino acids 183 to 195 of the human proET-1 sequence (SEQ ID NO: 18). 
     
     
         20 . The method according to  claim 1 , wherein patients are stratified for therapeutic treatment. 
     
     
         21 . The method according to  claim 20 , wherein the patients are stratified according to their need of a cardiac pacemaker by determining the level of CT-proET-1, wherein a level below a predetermined threshold level is indicative of patients suffering from orthostatic hypotension who do not need a cardiac pacemaker, and wherein a level above a predetermined threshold level is indicative of patients suffering from cardioinhibitory reflex who are in need of a cardiac pacemaker. 
     
     
         22 . The use of one or more biomarkers selected from the group consisting of proADM, proANP, proBNP, proAVP, proET-1 and PCT or a fragment of at least 12 amino acids thereof for the diagnosis and/or prognosis and/or assessment and/or therapy stratification of syncope.